Nanotechnology holds great potential, and nanomaterials are increasingly being developed for use in industrial, military, and consumer products including a vast array of biomedical applications. Gold nanorods (GNRs) are of particular interest due to their unique optical region absorbance, emission, and electronic properties. Based on these unique characteristics, GNRs have been used in a vast array of biomedical applications. However, the combination of responses from GNRs including elicited toxicity, poor cellular uptake, and loss of NIR optical properties due to intracellular aggregation remain obstacles for nanobased biomedical applications. The toxicity of GNRs is known largely to be due to free and surface-associated cetyl trimethylammonium bromide (CTAB), a cationic surfactant used in the aqueous synthesis of GNRs. Two main strategies have been reported to overcome this surfactant's cytotoxicity: replacement by post-synthesis ligand exchange or noncovalent overcoating by chemical cover layering through electrostatic attraction. Unfortunately, some commonly used surface modifications, for example, polyethylene glycol (PEG) functionalization, can significantly lower cellular uptake of the GNRs into cells, reducing their use in biomedical applications. Furthermore, overcoatings can break down in biological environments over time, resulting in surface leaching of the CTAB, so chemical stabilization by overcoating does not guarantee that the CTAB toxicity is completely mitigated.
Previous studies have reported that TA-coated (tannic acid) GNRs (MTAB-TA GNRs) show reduced toxicity, demonstrate a distinctive form of endosomnal uptake, and display a unique intracellular distribution pattern that reduces particle aggregation. Unfortunately, as the CTAB-TA GNR's aspect ratio (AR) increases, so does the toxicity, possibly due to the remaining CTAB.
To lower the toxicity of the GNRs, the removal or exchange of the CTAB from the GNRs may be performed, e.g. with MTAB. GNRs coated with MTAB (11-mercaptoundecyltrimethylammonium bromide) have been synthesized, but limited information is available in terms of their biocompatibility and characterization within biological matrices. However, it was found that 40% of the MTAB GNRs were taken up by the cells, compared to less than 1% of their PEGylated analogs, exceeding the previously-reported GNR uptake values. However, published TEM (transmission electron microscopy) images showed extensive aggregation of intracellular particles (GNRs), causing a loss of their near infrared (NIR) optical priorities. In particular, the intracellular features exhibited close proximity side-by-side assembly of GNRs, which can result in blue shift of plasmon resonance emissions moving the GNRs spectra out of the target NIR “water window” needed for biomedical applications.
Thus there remains a need for methods of synthesizing gold nanorods (GNRs) with enhanced biocompatibility and cellular uptake, while preventing particle aggregation to preserve key NIR optical properties.